BRPI1005537A2 - iron bisglycinate chelate - Google Patents

Abstract

IRON BIS GLYCINATE CHELATE. The present invention relates to iron bisglycinate chelate for use in the oral treatment of anemia in celiac patients. In particular, in solid oral forms, the iron bisglycinate chelate according to the invention is administered in an amount ranging from 5 to 200 per day (corresponding to 1 to 40 mg of iron ion), preferably from 10 to 100 mg per day (ie corresponding to 2 to 20 mg iron ion). In semisolid and liquid forms, the iron bisglycinate chelate according to the invention is administered in an amount ranging from 3 to 6 g / 100 ml solution (corresponding to 6 to 12 mg iron ion / ml), preferably about 5g / 100ml solution (corresponding to 10 mg iron ion / ml)

Description

"IR BIS GLYCINATE CHELATE"

The present invention relates to iron bisglycinate chelate for use in the oral treatment of anemia in celiac patients. Foundations of the Invention

Celiac disease is a small bowel disease with immediate-immune pathogenesis characterized by permanent intolerance to protein fractions of wheat, rye, barley and oats. In genetically pre-disposed individuals, such intolerance causes a mucosal breakdown, which in turn leads to small bowel atrophy (Farhad Zamani et al., Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin World J. Gastroenterol. 2008 14 (48), 7381-7385).

Celiac disease affects both adult individuals and the pediatric population. Indeed, celiac disease is one of the most common causes of malabsorption, especially in the pediatric age, where it is considered one of the diseases most often capable of retarding growth.

Generally, the clinical manifestations of this disease have a high individual variability and they are only and partially conditioned by the degree of lesions involving the small intestine (Fernando Bermejo et al. Gastroenterol, 2009, 15 (37) 46387-4643).

For this reason, there are conditions of extreme heterogeneity ranging from forms with severe malformation syndrome to almost asymptomatic forms. In this context, it should be noted that celiac disease causes a change in both number and shape of intestinal villus, whereby absorption of exogenous substances and / or nutrients occurs.

Celiac disease in various symptoms and each of them is present in celiac individuals at different percentages (Jason W. Harper et al. Anemia in Celiac disease is multifactorial in etiology Am. J. Hematol. 2007, 82, 996-1000).

Some clinical manifestations, or symptoms, present in celiac patients in varying degrees of seriousness include: weight loss, asthenia, nausea, vomiting, coagulation disorder, osteopathy with bone pain, profuse mucosity, especially regarding the tongue, and neurological disorders of the nervous system. (Farhad Zamani et al., Gluten sesitive enteropathy in patients with iron deficiency anemia of unknown origin World. Gastroenterol 2008, 14 (48), 7881; Freeman H. et al. Coeliac disease Best. Pract. Res. Clin. Gastroent. 2002, 16 (1), 37-49). Another obvious symptom of celiac disease is diarrhea, whose etiopathogenesis is multifactorial.

One of the causes of diarrhea is food malabsorption, which results in increased intraluminal stool content, which, having a high osmotic capacity, has a higher volume with respect to physiological conditions. Poor digestion is another cause that results in the formation of diarrhea. Indeed, a reduction in cholecystokinin and secretion secretion are observed in celiac patients, which results in non-digestion of proteins and lipids.

In addition, one of the most significant signs common to about 50% of celiac disease patients is sideropenic anemia, observable by the reduction in hemoglobin, ferritin, and blood iron content following hemochromocytometric testing.

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It is well known that in celiac patients, this anemia cannot be

treated by oral therapy based on compounds containing iron ions in the form of salts, complexes and other substances separated at the gastroenteric level. Indeed, according to literature descriptions, oral treatment using iron-containing compounds does not cause an increase in hemoglobin / iron values in the blood of celiac patients (Fernandez-Banares et al. A short review of malabsorption and anemia World J. Gastroenterol, 2009 15 (37): 4464-4652). Thus far, consolidated therapy for anemia in celiac patients consists of parenteral, particularly intravenous, administration of iron salts, such as, for example, glyconate in repeated therapeutic cycles every 4 or 6 months, depending on the severity of the anemia. So far, only this method of administration provides the therapeutic benefit required for patients affected by said condition. Currently, oral iron salt-based treatment has been considered useful only as a supplement at the stage of maintaining hemoglobin blood values following parenteral treatment.

The method of parenteral administration is very often patient-deprecated and particularly disadvantageous, as it requires the intervention of medical personnel specializing in appropriate health facilities or hospitalization of the patient in order to control possible anaphylactic reactions.

Thus, there is a strong need to find a suitable therapeutic solution to treat anemia in celiac patients, capable of improving patients' compliance with treatment. DESCRIPTION OF THE INVENTION

It has surprisingly been found that iron bisglycinate chelate, administered orally to celiac patients, causes a considerable increase in blood serum hemoglobin, ferritin and iron levels and can thus be used effectively to treat anemia.

This compound and its structural formula I, given below, are well known (Ashmed SD The Chemistry of iron bis-glycinate chelate, Arch Latino Am. De Nutr., 2001, 51 (1), 7-12; Atkins PW Berau JA , 1992 General Chemistry 2nd ed., Scientific American Books, Wh Freeman New York; Coplin et al .. Tolerability of Iron: a comparison of bis-glycino iron II and ferrous sulphate, Clinical Therapeutics, vol 13, η.5, 604- 612, 1991). Iron bis-glycidinate chelate is a somewhat soluble chelate complex, characterized by a metal center, Fe (II), tetracoordinated by two identical chelating agents (glycine) and corresponds to the following structural formula I:

(Yy0

The

(I)

The dative bonding of nitrogen atoms contributes to stabilize the energy of the metallic center orbitals and the bonding agent geometry by forming a five-atom ring.

This compound is also known for its tolerability, safety and high bioavailability (Jeppsen RB Toxicology and safety of Ferrochel and other iron amino acids chelates, Arek Latino Am. De Nutr., 2001, 51 (1), 26 - 34; Scientific Panel on Food Additives, Flavoring Processing Aids Processing and food contact materials in a Commission request concerning: ferrous bisglycinate as an iron source for use in food manufacturing and food supplements, EFSA Journal , 2006, 299-1-17).

Literature data show that such chelate complex has a greater bioavailability with respect to mineral salts, such as, for example, ferrous sulfate, because it is absorbed as it is at the level of the intestinal mucosa and thus does not undergo any modification in the Gastrointestinal system (Pineda O. et al., Effectiveness of iron amino acids chelate on treatment of iron deficiency anemia in adolescents, Journal of Appl. Nutr., Vol. 46, Numbers 1 - 2, 1994; Pineda O., Effectiveness of treatment of iron deficiency anemia in children and young children with ferrous bisglicinate chelate, Nutrition, 2001, 17, 381-384). Binding stability, proven by the fact that the product does not hydrolyze at different pH values of the gastrointestinal section and the high molecular weight (204 Daltons) allow for maximum absorption when administered orally (DeWayne HA, The absorption and metabolism of iron amino). acid chelate, Arck Latin Am. De Nutr., 2001, 51 (1), 7-12; Marchetti M et al., Comparison of the rates of vitaminic degradation when mixed with metal sulphates or metal amino acid chelates, J. Food Comp Anal, 2000, 13 (875-884).

Thus, the aim of the present invention is iron bisglycinate chelate for use in the oral treatment of anemia in celiac patients.

In accordance with the present invention, the term "celiac patient" is used to denote a human being as both an adult and a "pediatric population" where the term "pediatric population" denotes the part of the population from birth to eighteen deity.

The term "anemia" according to the present invention comprises: sideropenic anemia, aplastic anemia, vitamins and / or folate deficiency anemia (such as, for example, pernicious anemia), anemia of chronic diseases (such as, for example, AIDS, cancer or hepatitis) and hemolytic anemia.

From the therapeutic efficiency results summarized in the present invention (given below in the examples and the experimental part) obtained by celiac patients suffering from iron bisglycinate chelate anemia, it can be argued that the chemical / physical characteristics of bisglycinate chelate such as low molecular weight and the absence of electric charges represent a positive element for absorption through the modified intestinal villi observed in most celiac patients. Contrary to conventional iron salts taken orally, iron bis-glycinate chelate is not separated into iron ions within a pH range of 3 to 10.

In contrast, conventional iron salts taken orally, for example ferrous sulfate, are separated at the gastrointestinal level into iron ion and corresponding anion. Fe ++, having positive charges, is poorly absorbed by the modified intestinal villus.

Preferably, the iron bisglycinate chelate of the invention is intended for use for oral treatment of sideropenic anemia in celiac patients.

Sideropenic anemia is a form of anemia characterized by a considerable reduction in circulating blood hemoglobin caused by iron deficiency. The use of iron bisglycinate chelate for the oral treatment of this type of anemia is thus particularly advantageous in that iron bisglycinate chelate according to the present invention can be considered a screening substance to be used. in patients with sideropenic anemia, even persistent and / or in the presence of gluten free diets.

In particular, iron bisglycinate according to the present invention, i.e. tablet, preferably effervescent tablet or semi-solid or liquid form, is more easily absorbed by the modified intestinal villus of a celiac patient with respect to other conventional pharmaceutical forms.

The iron bisglycinate chelate according to the present invention is thus orally administered, preferably formulated in solid, semi-solid or liquid form, said form being selected from tablet, granulate, micro-granule or capsule and said semi-solid or non-solid form. liquid selected from suspension or solution.

The iron bisglycinate chelate of the invention may be formulated in association with at least one sweetener and / or flavoring. Preferably, the ratio between said at least one sweetener and / or flavoring and the iron bisglycinate chelate of the invention is equivalent to about 0.56 by weight.

Said at least one sweetener and / or flavoring according to the present invention may preferably be selected from acesulfame K, sacralose, sorbitol, sucrose, fructose, orange flavor, lemon flavor, mandarin flavor, caramel flavor or a mixture thereof. .

More particularly, the iron bisglycinate chelate of the present invention is preferably formulated associated with a mixture comprising acesulfame K, sacralose, sorbitol and flavorant, where the weight ratio of acesulfame K1: sacralose: sorbitol: flavor is about 1: 0.30 - 0.50: 0.12 - 0.24: 3.0-3.4, respectively, preferably from about 1: 0.40: 0.18: 3.20 by weight. According to the present invention, iron bisglycinate chelate may further be formulated in combination with other physiologically acceptable excipients and / or additives.

According to the invention, tablet, granulate and micro-granules may be in coated, uncoated and / or effervescent form, preferably in effervescent tablet form.

The term "effervescent" according to the present invention is used to indicate a form capable of developing carbon dioxide on contact with water and / or the oral environment in the presence of saliva.

The di, tricarboxylic acids or a mixture thereof are preferably used to obtain the effervescent form of the invention.

More preferably, the effervescent compositions according to the present invention are formulated using sodium citrate dihydrate and monohydrate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid, adipic acid, monosodium phosphate, alginic acid, hydrocarbonate. of magnesium or a mixture of them. In particular, in oral solid forms, the iron bisglycinate chelate according to the present invention is contained in an amount ranging from 5 to 200 mg iron bisglycinate chelate (corresponding to 1 to 40 mg of iron ion), preferably from 10 to 100 mg (i.e. corresponding to from 2 to 20 mg iron ion).

Preferably, the iron bisglycinate chelate is contained in an amount equivalent to about 70 mg for effervescent tablet (i.e., corresponding to about 14 mg of iron ion).

A preferred embodiment of the invention comprises administering iron bisglycinate chelate by two effervescent tablets per day containing about 70 mg iron bis glycinate chelate (i.e. 14 mg iron ion) per twenty days

Another embodiment of the invention comprises the administration of iron bisglycinate chelate by two effervescent tablets per day containing 70 mg iron bisglycinate chelate (i.e. 14 mg iron ion) wax per twenty days and one effervescent tablet per day containing 70 mg iron bisglycinate chelate (ie 14 mg iron ion) for a further 40 days ("course of therapy").

Each course of therapy according to the present invention may be repeated every 3-4 months for a total period of about one year.

Another embodiment of the invention comprises administering iron bisglycinate chelate by two effervescent tablets per day containing about 70 mg iron bis glycinate chelate (i.e. 14 mg iron ion) for twenty days, one effervescent tablet per day containing about 709 mg iron bisglycinate chelate (ie 4 mg iron ion) for a further forty days ("therapy cycle") and a maintenance therapy with 2 tablets. effervescent drinks per day containing about 70 mg bisglycinate chelate (ie 14 mg iron ion) for twenty days ("maintenance"). Maintenance in accordance with the present invention may be repeated every 3 months for a total period of time of about one year. The term "maintenance" of the invention is used to indicate continuation of therapy, with possible increase in hemoglobin, ferritin and serum iron values.

In semisolid or liquid forms, the iron bisglycinate chelate according to the present invention is contained in an amount ranging from 1 to 10 g / 100 ml solution / suspension (corresponding to 2 to mg iron ion ka / ml, preferably about 5 g / 100 ml solution / suspension (corresponding to 10 mg iron ion / ml).

Said semi-solid or liquid forms of the invention are preferably administered to the pediatric population, preferably in aqueous solution form. Thus, another embodiment of the invention comprises administering iron bisglycinate chelate to the pediatric population in aqueous solution via a dropper calibrated to 0.5 ml, 0.75 ml and 1 ml to allow adapt the dosage according to age, weight and possibly to the severity of celiac disease.

According to another embodiment, the iron bisglycinate chelate of the invention may be administered in association with one or more other active ingredients.

Other active ingredients according to the present invention according to the present invention may preferably be selected from vitamins and / or mineral salts.

Said vitamins may preferably be selected from vitamin B9 (folic acid), vitamin B12 and / or vitamin B6.

Said mineral salts may preferably be selected from salts of potassium, magnesium, iodine, zinc.

Iron bisglycinate according to the present invention may be administered as a single therapy or following therapy.

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conventional oral and parenteral therapy.

The following examples are intended for a better understanding of the invention without limiting it in any way whatsoever. EXAMPLES

Example 1: Effervescent Tablet Formulation

Active Ingredient mg / tablet

Iron bisglycinate chelate 70 mg (corresponding to

14 mg iron ion)

Effervescence Excipient

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Citric acid

Sodium bicarbonate

Sweeteners

Acesulfame K:

Sacralose

Sorbitol

Flavor

Orange Flavor

433 mg 307 mg

mg IOmg 4.5 mg

80 mg

The ratio of acesulfame K: sacralose: sorbitol: flavoring of the effervescent tablet of Example 1 is 1: 04.4: 0.18: 3.20.

The pH of the reconstituted solution by dissolving the effervescent tablet of Example 1 in 150 ml of water is 4.7. Examples 2 - 5: Formulation in aqueous solution Table A

COMPONENT SOLUTION Ll SOLUTION L2 SOLUTION L3 SOLUTION L4 Iron bisglycinate chelate 5.0 g 5.0 g 5.0 g 5.0 g fructose 38.5 g 38.5 g - - Sorbitol 30.8 g 30, 8 g 30.8 g 30.8 g citric acid 1.5 g 1.5 g 1.5 g 1.5 g Caramel flavor 1.4 g - 1.4 g - Tangerine flavor - 3.0 g - 3.0 g Sucrose - - 38.5 g 38.5 g Acesulfame K - - - 0.5 g Water qb at 100 ml q.s. at 100 ml q.s. at 100 ml q.s. to 100 ml PH 4.14 4.17 4.14 4.16

Experimental Part

a) Efficiency comparison between orally administered iron bisglycinate chelate according to the present invention and conventional treatment of the celiac patient.

Twelve individuals with sideropenic anemia diagnosed according to the hemoglobin (Hb) 5 ferritin and iron (serum iron) values obtained by the hemochromocytometric test were included in this experiment.

Celiac disease was diagnosed according to the

clinical manifestations and histology reports concerning the intestinal mucosa.

All patients were initially treated with orally ferrous sulphate (1 ferrous sulphate tablet, corresponding to 105 mg of

iron ion) for 40 days and / or with sodium ferric glyconate by intravenous administration for a variable period of time according to the severity of anemic status.

Both of these therapies were discontinued because they were inefficient and / or not tolerated.

Examples 6-11 indicate the clinical records of some

of celiac patients undergoing treatment using conventional iron salts by both oral (p.o.) and intravenous (i.v.) administration. All patients were diagnosed with celiac disease through biotic sampling and serological testing. During conventional therapy, the diet of these patients was controlled and corrected with gluten free foods. As evidenced by the following examples 6-11 which follow, regardless of treatment and diet, serum hemoglobin, ferritin and iron values remained considerably low.

These patients were then subjected to therapy using the iron bisglycinate chelate according to the present invention formulated on the effervescent tablet of example 1.

The hemoglobin (Hb), (Table 1), ferritin (Table 2) and serum iron (Table 3) values taken from each treated patient, both after conventional (oral and / or intravenous) therapy and after oral administration of according to the present invention (effervescent tablet) were considered for evaluation.

One course of therapy corresponds to treatment for 20 days with two effervescent tablets per day containing about 14 mg iron ion per tablet and then one effervescent tablet per day containing 14 mg iron ion for a further 40 days.

Subsequent maintenance corresponds to treatment for 20 days with two effervescent tablets per day containing 14 mg iron ion per day every 3 months for about one year.

During treatment, patients stated that they prefer oral treatment over parenteral treatment.

The product did not reveal any adverse effects worth mentioning.

Blood serum hemoglobin, ferritin and iron were determined after the first course of treatment and treatment was continued with repeated cycles according to the methods indicated above.

As noted by the values shown in Tables 1, 2 and 3, iron bisglycinate chelate considerably increased serum hemoglobin, ferritin and iron values after 1 cycle of therapy.

Thus, experimental data show the efficiency of therapy.

orally using iron bisglycinate chelate of the invention in the treatment of anemia in celiac patients, a condition in which all compounds administered orally to date have proven ineffective. Example 6 Patient I - Female Previous Therapies

Type Date Duration Reason for suspension Sulphate Fe p.o. 4 years A few days from time to time Gastrointestinal intolerance resulting in poor efficiency Ferric sodium gluconate iv (Ferric Fe) 3 years Cycles 15/18 days every 3-4 months, with 1-2 vials / day in 250 ml NaCl Occurrence of allergy (sudden skin attack)

At the beginning of ferrous sulfate therapy by administration

oral, the patient has the following values:

Hb Iron in serum Ferritin Duration of treatment Initial values 10.2 41 32 40 days Final values IU 48 38

The treatment cycle has been completed, but epistralgia and intestinal disorders have occurred.

After other cycles with ferrous sulfate administered

orally, interrupted due to intestinal intolerance, the patient undergoes oral treatment with iron polymaltosate.

Hb Serum iron Ferritin Treatment duration Initial values 10.6 38 29 20 days Final values 10.8 43 25

The treatment cycle is completed and the therapy well tolerated.

During therapy with some iron polymaltosate cycles

orally administered alternating with those with orally administered ferrous sulphate, Hb values were maintained between 9 and 10 gr / dl with occurrence of metrorrhagia and Hg reduction to 7.7.

Beginning of treatment with ferric iron i.v.

Hb Iron in serum Ferritin Duration of treatment Initial values 7.7 19 <5 20 days Final values 9.8 48 30 -

The treatment cycle was completed with a dosage of 1

vial / day for 10 days, then 2 vials / day.

The patient continued with intravenous iron administration.

once every three / four months, keeping Hb values between 11 and 13. Following the sudden onset of skin attack following ferric iron infusion, therapy was discontinued. Example 7 Patient II - Female Previous Therapies

Type Date (years) Duration Reason for suspension sulphate Fe p.o. 5 years, several attempts a few days Gastrointestinal intolerance Ferric sodium i.v. glyconate (Ferric Fe) 2 years, 2 cycles of 10 vials 10 days at different periods Rare efficiency due to incongruent dosing

At the beginning of ferrous sulfate therapy administered

orally the patient had the following values:

Hb Serum iron Ferritin Treatment duration Initial values 11.6 55 41 8/10 days Final values 12.3 68 45

A 40-day course of treatment was never completed due to the occurrence of severe epigastric pain after a few days.

Subsequently, the patient was given other iron formulations orally with the following results:

Hb Iron in serum Ferritin Duration of treatment Initial values 11.0 47 29 A few days Final values 11.5 56 33

A 40-day course of treatment has never been completed due to the occurrence of severe epigastric pain after a few days. Hb values were kept around 11 gr / d. Beginning of iron treatment by administration

intravenous:

Hb Iron in serum Ferritin Duration of treatment Initial values 10.4 40 31 some days Final values 10.8 49 33

The treatment cycle has not been completed due to fear of

infusion needle and working difficulty of the patient. Example 8

Patient III - Male - Vegetarian Patient

Previous Therapies

Type Date (years) Duration Reason for suspension sulphate Fe p.o. 5 years One-month cycles instead of how little Efficiency Ferric sodium i.v. glyconate (Ferric Fe) never given Poor treatment consent i.v. denied by patient

At the beginning of ferrous sulfate therapy administered

orally the patient has the following values:

Hb Iron in serum Ferritin Duration of treatment Initial values 9.1 32 19 40 days Final values 10 38 27

The treatment cycle was completed with strong

epigastric pain and intestinal disorders.

The patient never accepted the disease, did not take adequate iron dosages, and did not follow the diet correctly. Example 9 Patient IV - Female

Previous Therapies

Type Date (years) Duration Reason for suspension sulphate Fe p.o. never took i.v. sodium ferric glyconate (Ferric Fe) 3 years 15/20 day cycles with 1 i.v. bottle Poor efficiency at first and then intolerance occurred.

Orally administered ferrous sulphate never taken by

patient due to serious gastrointestinal disorders (gastric ulcers and irritable colon). Initiation of iron ferric therapy by administration

intravenous:

Hb Iron in serum Ferritin Duration of treatment Initial values 9.7 39 21 20 days Final values 10.6 54 42

Treatment cycle completed with 1 vial dosing / day

for 10 days, then 2 vials / day. The patient continued with iron by intravenous administration.

with cycles every 3 to 4 months, with Hb values around 11 gr / dl. Suspended therapy due to sudden skin attack and asthmatic attack following intravenous iron infusion. Example 10 Patient V - Female

Previous Therapies

Type Date (years) Duration Reason for suspension sulphate Fe p.o. Several 30/40 day attempts Poor efficiency and occurrence of gastrointestinal disturbances Ferric sodium glyconate i.v. (Ferric Fe) Only one cycle Some days Suspended due to allergy

After several cycles of ferrous sulphate therapy

administered orally, the patient has the following values:

Hb Iron in serum Ferritin Duration of treatment Initial values 8.4 22 <5 40 days Final values 9.7 46 21

Due to intestinal disorders observed in the patient, the

Iron therapy by intravenous administration was attempted. Suspended after three infusions due to an allergic reaction. Example 11

Patient VI - Male

Previous Therapies

Type Date (years) Duration Reason for suspension Sulphate Fe p.o. 1 year a few days intestinal disorders (diarrhea) Ferric sodium glyconate i.v. (Ferric Fe) 2 years 3 20-day cycles with 1 vial i.v. in 250 ml saline Occurrence of intolerance in the third cycle (phlebopathy)

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Orally administered ferrous sulphate therapy, discontinued due to the occurrence of profuse diarrhea after a few days. Therapy start

with iron by intravenous administration.

Hb Iron in serum Ferritin Duration of treatment Initial values 10.2 41 35 20 days Final values 12.6 68 81

Occurrence of phlebopathy during infusion after the third

treatment cycle.

Table 1: Hemoglobin values after oral ferrous sulfate treatment and / or intravenous ferric sodium glyconate treatment with respect to

oral treatment with the effervescent tablet of example 1.

Pte / Gender Initial Therapy Suspension Ratio Hb Values (g / 100 ml) Effervescent Tablet Therapy * 1st Cycle Hb Values (g / ioo ml) tab. effervescent Hb value (g / ml) 1 / F 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 9.1 Iron bisglycinate chelate 11.8 Iron bisglycinate chelate 12.3 2 / F 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 9.9 Iron bisglycinate chelate 12.3 Iron bisglycinate chelate 12.9 3 / F 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance and poor efficacy 10.3 Iron bisglycinate chelate 12.7 Iron bisglycinate chelate 13.1 4 / M Fe Sulphate Fe p.o. Inefficiency 8.9 Iron bisglycinate chelate 11.9 Iron bisglycinate chelate 12.7 5 / F sodium ferric glyconate iv Intolerance and inefficiency 10.4 Iron bisglycinate chelate 12.1 Iron bisglycinate chelate 12.1 iron glycinate 13,4 6 / F 1) Sulphate Fe po 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 8.6 Iron bisglycinate chelate 10.0 Iron bisglycinate chelate 12.1 7 / F Sulphate Fe p.o. Patient inefficiency and intolerance 11.1 Iron bisglycinate chelate 12.5 Iron bisglycinate chelate 13.6 8 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 10.9 Iron bisglycinate chelate 12.0 Iron bisglycinate chelate 12.9 9 / M 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 11.8 Iron bisglycinate chelate 13.1 Iron bisglycinate chelate 14.3 10 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) inefficiency 2) intolerance 10.2 iron bisglycinate chelate 11.7 iron bisglycinate chelate 13.4 1 l / F 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 9.9 Iron bisglycinate chelate 12.0 Iron bisglycinate chelate 13.2 12 / M 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. 1) Inefficiency 2) Intolerance 11.1 Iron bisglycinate chelate 12.8 Iron bisglycinate chelate 14.0

* two effervescent tablets per day for 20 days, then one tablet per day for 40 days. ** Two effervescent tablets a day for 20 days every 3 months for about a year. 0 The patient followed a vegetarian diet.

Ferritin values following oral ferrous sulfate treatment and / or intravenous treatment with ferric sodium gluconate with respect to oral treatment with the effervescent tablet of example 1.

Pte / Gender Initial Therapy Suspension Ratio Hb Values (g / ioo ml) Effervescent Tablet Therapy * 1st Cycle Hb Values (g / ioo ml) tab. effervescent ** Hb value (g / 100 ml) l / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 20 Iron bisglycinate chelate 121 Iron bisglycinate chelate 147 2 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 28 Iron bisglycinate chelate 101 Iron bisglycinate chelate 146 3 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance and poor efficiency 18 Iron bisglycinate chelate 111 Iron bisglycinate chelate 177 4 / M Fe sulphate p.o. Inefficiency <5 Iron bisglycinate chelate 43 Iron bisglycinate chelate 92 5 / F sodium ferric glyconate iv Intolerance and inefficiency 22 Iron bisglycinate chelate 100 Iron bisglycinate chelate 143 6 / F 1) Fe po sulphate 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 7 Iron bisglycinate chelate 63 Iron bisglycinate chelate 79 7 / F Fe sulphate p.o. Patient inefficiency and intolerance 23 Iron bisglycinate chelate 80 Iron bisglycinate chelate 193 8 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 20 Iron bisglycinate chelate 96 Iron bisglycinate chelate 134 9 / M 1) Fe sulphate p.o. 2) Ferric sodium glyconate i.v. D Inefficiency 2) Intolerance 27 Iron bisglycinate chelate 119 Iron bisglycinate chelate 206 10 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 14 Iron bisglycinate chelate 54 Iron bisglycinate chelate 127 1 l / F 1) Fe sulphate p.o. 2) sodium ferric glyconate i.v. D Inefficiency 2) Intolerance 12 Iron bisglycinate chelate 78 Iron bisglycinate chelate 151 12 / M 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 24 Iron bisglycinate chelate 67 Iron bisglycinate chelate 200

* two effervescent tablets per day for 20 days, then one tablet per day for 40 days. ** Two effervescent tablets a day for 20 days every 3 months for about a year. 0 The patient followed a vegetarian diet.

Serum iron values following oral ferrous sulfate treatment and / or intravenous ferric sodium glyconate treatment with respect to oral treatment with the effervescent tablet of Example 1.

Pt / sex Initial therapy Reason for suspension Serum iron values (mcg / dl) Tablet effervesc therapy. serum iron values (mcg / dl) Maintenance tab. effervescent Serum iron values (mcg / dl) l / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 27 Iron bisglycinate chelate 64 Iron bisglycinate chelate 71 2 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 31 Iron bisglycinate chelate 70 Iron bisglycinate chelate 77 3 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance and poor efficiency 39 Iron bisglycinate chelate 92 Iron bisglycinate chelate 84 4 / M Fe sulphate p.o. Inefficiency 16 Iron bisglycinate chelate 56 Iron bisglycinate chelate 68 5 / F Sodium ferric glyconate iv Intolerance and inefficiency 30 Iron bisglycinate chelate 65 Iron bisglycinate chelate 78 6 / F 1 ) Fe po sulphate 2) Ferric sodium glyconate iv 1) Inefficiency 2) Intolerance 19 Iron bisglycinate chelate 44 Iron bisglycinate chelate 51 7 / F Fe sulphate ρ, ο, Patient inefficiency and intolerance 34 Bischelate chelate iron glycinate 62 Iron bisglycinate chelate 67 8 / F 1) Fe sulphate 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 29 Iron bisglycinate chelate 48 Iron bisglycinate chelate 51 9 / M 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 32 Iron bisglycinate chelate 73 Iron bisglycinate chelate 87 10 / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 33 Iron bisglycinate chelate 41 Iron bisglycinate chelate 80 1 l / F 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) Inefficiency 2) Intolerance 25 Iron bisglycinate chelate 57 Iron bisglycinate chelate 93 12 / M 1) Fe sulphate p.o. 2) i.v. ferric sodium glyconate 1) inefficiency 2) intolerance 32 iron bisglycinate chelate 61 iron bisglycinate chelate 103

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* two effervescent tablets per day for 20 days, then one tablet per day for 40 days. ** Two effervescent tablets a day for 20 days every 3 months for about a year. - 0 The patient followed a vegetarian diet.

Conclusion

Thus, as evidenced by the examples and tables given above, only oral iron bisglycinate chelate therapy according to the present invention allowed a considerable increase in the blood parameters examined (serum iron, ferritin, hemoglobin) in celiac patients suffering anemia and eliminating adverse effects (gastrointestinal or otherwise) due to ingestion of conventional iron salts by oral or intravenous administration.

When iron bisglycinate chelate therapy according to the present invention was carried out it could be assumed, according to known data, that the product could reveal better tolerance, but such significant efficiency results were totally unexpected.

Claims (11)

1. Iron bisglycinate chelate, characterized in that it is for use in the oral treatment of anemia in patients affected by celiac disease in the form of a tablet or in semi-solid or liquid form. Iron bisglycinate chelate according to claim 1, characterized in that said tablet is an effervescent tablet. Iron bisglycinate chelate according to either of claims 1 or 2, characterized in that said tablet contains an amount ranging from 1 mg to 40 mg of iron ion, preferably from 2 to 20 mg of iron ion. Iron bisglycinate chelate according to claim 3, characterized in that said tablet contains an amount equivalent to about 14 mg of iron ion. Iron bisglycinate chelate according to any one of claims 1 to 4, characterized in that it is administered by two effervescent tablets per day containing about 14 mg iron ion per tablet for twenty days. Iron bisglycinate chelate according to any one of claims 1 to 5, characterized in that it is administered by two effervescent tablets per day containing about 14 mg iron ion per tablet for twenty days and one effervescent tablet containing about 14 mg of iron ion for a further forty days. Iron bisglycinate chelate according to claim 1, characterized in that said semi-solid or liquid form is selected from suspension or solution. Iron bisglycinate chelate according to claim 7, characterized in that said semi-solid or liquid form contains an amount ranging from 6 to 12 mg iron ion / ml, preferably about 10 mg iron ion / ml. . Iron bisglycinate chelate according to any one of the preceding claims, characterized in that said iron bisglycinate chelate is formulated in association with at least one sweetener and / or flavoring. Iron bisglycinate chelate according to any one of the preceding claims, characterized in that said iron bisglycinate chelate is administered in association with at least one other active ingredient. Iron bisglycinate chelate according to claim 1, characterized in that said anemia is sideropenic anemia.